Needleless injector

ABSTRACT

An injector includes a housing having a chamber for holding a liquid formulation of an active principle to be injected into a biological body and an output port in fluid communication with the chamber through which the liquid formulation is injected. A piston is positioned within the housing, and includes an end portion with substantially the same shape as the chamber. A magnetic force draws the piston and housing together to expel the liquid formulation out of the chamber through the output port.

RELATED APPLICATION

This application claims the benefit of U.S. Provisional Application No.60/338,169, filed Oct. 26, 2001, the entire contents of which areincorporated herein by reference.

BACKGROUND

Injection of a liquid such as a drug into a human patient or anagriculture animal is performed in a number of ways. One of the easiestmethods for drug delivery is through the skin which is the outermostprotective layer of the body. It is composed of the epidermis, includingthe stratum corneum, the stratum granulosum, the stratum spinosum, andthe stratum basale, and the dermis, containing, among other things, thecapillary layer. The stratum corneum is a tough, scaly layer made ofdead cell tissue. It extends around 10-20 microns from the skin surfaceand has no blood supply. Because of the density of this layer of cells,moving compounds across the skin, either into or out of the body, can bevery difficult.

The current technology for delivering local pharmaceuticals through theskin includes methods that use needles or other skin piercing devices.Invasive procedures, such as use of needles or lances, effectivelyovercome the barrier function of the stratum corneum. However, thesemethods suffer from several major disadvantages: local skin damage,bleeding, and risk of infection at the injection site, and creation ofcontaminated needles or lances that must be disposed of. Further, whenthese devices are used to inject drugs in agriculture animals, theneedles break off from time to time and remain embedded in the animal.

Thus, it would be advantageous to be able to inject small, precisevolumes of pharmaceuticals quickly through the skin without thepotential of a needle breaking off in the animal.

SUMMARY

Some have proposed using needleless devices to effectively deliver drugsto a biological body. For example, in some of these proposed devices,pressurized gas is used to expel a drug from a chamber into the body. Inanother device, a cocked spring is released which then imparts a forceon a chamber to expel the drug. In these types of devices, however, thepressure applied to the drug decreases as the gas expands or the springextends. It is desirable, however, for the injection pressure to remainthe same or increase during the injection period.

In one aspect of the invention, an injector includes a housing having achamber for holding a liquid formulation of an active principle to beinjected into a biological body and an output port in fluidcommunication with the chamber through which the liquid formulation isinjected. A piston is positioned within the housing, and includes an endportion with substantially the same shape as the chamber. A magneticforce draws the piston and housing together to expel the liquidformulation out of the chamber through the output port.

Embodiments of this aspect can include one or more of the followingfeatures. The output port can has a diameter of approximately 50 μm to200 μm, and the chamber can have a tapered shape. The injector includesan inlet port for filling the chamber with the liquid formulation. Theinjector includes an actuator attached to the piston and made of shapememory alloy. The actuator moves the piston away from the housing when apotential is applied to the actuator. When the potential is removed thepiston moves towards the housing. The actuator is a fiber of the shapememory alloy, and the shape memory alloy can be Ni—Ti. The shape memoryalloy is approximately 10 mm to 200 mm long, and it contractsapproximately 0.5 mm to 10 mm when the potential is applied to thealloy. The shape memory alloy structure changes phase from martensite toaustenite when the potential is applied to the alloy.

In some embodiments, the injector includes a capacitor that applies thepotential when it discharges. The capacitor has an energy output of atleast 10 J and can be approximately 100 J.

The injector has an injection pressure of at least 1 MPa and a maximuminjection pressure of approximately 300 MPa. In certain embodiments, theinjector has a cycle time of about one sec.

In another aspect of the invention, an actuator includes a contractingmaterial under tension produced by a magnetic force, and a capacitorwhich is able to discharge a potential to the fiber to cause the fiberto contract. The fiber relaxes to a stretched state when the potentialis removed. The contracting material can be a shape memory alloy or acontracting polymer or polymers, or any other suitable contractingmaterial.

In yet another aspect of the invention, a injector includes a housinghaving a chamber for holding a liquid formulation of an active principleto be injected into a biological body, and an output port in fluidcommunication with the chamber through which the liquid formulation isinjected. A piston is positioned within the housing, and includes an endportion with substantially the same shape as the chamber. An actuator isattached to the piston and made of shape memory alloy. The piston andhousing are drawn together by a magnetic force, and the actuator movesthe piston away from the housing when a potential is applied to theactuator, and the piston moves towards the housing when the voltage isremoved to expel the liquid formulation out of the chamber through theoutput port.

Related aspects of the invention include a method of injecting a liquidformulation of an active principle into a biological body with aninjector having one or more of the aforementioned features, and a methodof actuating a fiber of shape memory alloy.

Embodiments of this invention can have one or more of the followingadvantages. The injector is self-contained and portable. Since theinjection process is needleless, there are no needles that can break offand remain within the biological body. Since the injector can bere-charged at a rapid rate, a large number of animals can be injectedwith the liquid formulation over a short period of time. Further, sincethe injector contains enough liquid formulation for numerous injections,the operator is able to inject many animals with a single injectorbefore refilling a reservoir or a set of reservoirs or obtaining anotherinjector with a filled reservoir.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing and other objects, features and advantages of theinvention will be apparent from the following more particulardescription of preferred embodiments of the invention, as illustrated inthe accompanying drawings in which like reference characters refer tothe same parts throughout the different views. The drawings are notnecessarily to scale, emphasis instead being placed upon illustratingthe principles of the invention.

FIG. 1 is a side schematic view of a drug delivery device in accordancewith the invention.

FIG. 2A is a graph of the time response of a shape memory alloy actuatorof the drug delivery device of FIG. 1 for a high strain.

FIG. 2B is a graph of the time response of the shape memory alloyactuator when the actuator is subjected to a potential as a quick pulse.

DETAILED DESCRIPTION OF THE INVENTION

A description of preferred embodiments of the invention follows.

Referring to FIG. 1, there is shown a schematic view of a drug deliverydevice 10 which is used to inject a liquid formulation of an activeprinciple such as, for example, a drug into a biological body such as aagriculture animal. The drug is initially contained in a chamber 12 ofthe device and is injected out through an orifice 13 into the animal. Adrug reservoir 14 supplies the chamber 12 with sufficient amount of thedrug for each injection and holds enough of the drug for approximately20 to 200 or more injections. Alternatively, and particularly for usewith humans, individual doses may be provided in a plurality ofreservoirs sequentially coupled to the delivery device.

The device 10 includes a horn 18 in which a piston 20 is positioned. Oneend of an actuator 22 is attached to the piston 20, and the other end isattached to a surface 24. The surface 24 and the horn 18 are mounted ina manner, for example, within an applicator, such that the piston 20 isable to move back and forth in the direction of the double arrow Arelative to the horn 18 and the surface 24.

The horn 18 includes an outer housing 26 provided with an inlet port 28,a bore 30, and a tapered section 32. The piston 20 includes acylindrical section 34 spaced apart from the inner surface of the bore30 by a narrow gap, g, such as 50 μm to 250 μm, preferably 100 μm, toform a clearance seal, and an end section 36 having the same shape asthe tapered section 32 of the horn 18. The end section 36 of the pistonand the tapered section 32 of the horn define the chamber 12 whichreceives a desired amount of the drug from the reservoir 14 through theinlet port 28. A valve 38 is located within the inlet port 28, orbetween the port and the reservoir 14, and is opened and closed underthe direction of a controller 39, such as, for example, amicroprocessor, to allow the desired amount of drug into the chamber 12for each injection. Additionally, there is a ring seal 40 to prevent thedrug from escaping from the chamber 12 out between the horn 18 and thepiston 20.

The actuator 22 includes one to 10 or more fibers 42 arranged parallelto one another. One end 44 of the fibers 42 is attached to the surface24 with a clamp 46 and the other end 48 is attached to the piston 20with another clamp 50 so that the fibers 42 are under tension. Each ofthe fibers 42 is insulated from the other fibers along its length by aninsulating coating. Further, the ends 48 are insulated from each otherin the clamp 50, whereas the ends 44 are in electrical contact with eachother through the clamp 46. When a potential is applied to the ends 44,the fibers 42 contract to move the piston 20 away from the horn 18.

A class of materials that contact when a potential is applied to themincludes piezoelectric crystals and shape memory alloys. Whilepiezoelectric crystals contract about 1%, shape memory alloys are ableto contract approximately 5%. The larger contraction of shape memoryalloys make them desirable for the illustrated embodiment. Accordingly,the fibers 42 are made of a shape memory alloy such as, for example,Ni—Ti available under the Trade Mark Nitinol. When a potential from apower source 52, also under the direction of the controller 39, isapplied to the ends 44 of the fibers 42 the fibers heat up. As thefibers heat up, a phase transformation of the fiber material occurs,namely, the fiber changes from martensite to austenite. This phasetransformation causes the fibers 42 to contract such that the piston 20is pulled way from the horn 18. A more detailed description of shapememory alloys and their use is described in U.S. Pat. No. 5,092,901, thecontents of which are incorporated herein in its entirety.

In the presently discussed embodiment, the piston 20 and the taperedsection 32 of the horn 18 are permanent magnets such that the facingsurfaces of the tapered section 32 and the end section 36 are oppositelypolarized. Magnetic forces bring the horn and the piston rapidlytogether when the potential is removed to allow the fibers 42 to relax.Because the magnetic force is inversely related to the square of thedistance between the surfaces, the force rapidly increases through thestroke. By using permanent magnets rather than electromagnets, the largemass and power requirements of an electromagnet are avoided, although insome other embodiments, electromagnets are used. Also, in someembodiments, the tapered section 32 is a metal rather than a permanentmagnet.

The power source 52 includes a super capacitor 53 that is energized by aset of batteries 55. Accordingly, the potential is applied to the fibers42 when the super capacitor 53 discharges though a closed switch 56, andis removed when the super capacitor is being recharged with thebatteries 55. The power source 52 is also provided with an on/off switch57. Although any capacitor can be used to apply a potential to thefibers 42 when the capacitor discharges, a super capacitor has theadvantageous feature of providing a large energy density in a smallphysical size. The super capacitor 53 has a volume from 1.5 ml to 30 ml,preferably 3 ml, and an energy output of 10 J to 1 KJ, preferably 100 J.The current applied to the fibers 42 is approximately 100 mAmps to 5Amps, and the voltage applied to the fibers is between about 1 volt to10 volts. In one embodiment, the applied current is 1 Amp, and theapplied voltage is 5 volts.

The fibers 42 have a length, l₁, of approximately 10 mm to 200 mm,preferably 100 mm that when contracted pulls the piston 20 from the horn18 by a distance, l₂, of approximately 0.5 mm to 10 mm, preferably 5 mm.The fibers 42 can have circular cross section, in which case each fiber42 has a diameter of approximately 0.025 mm to 2 mm. Alternatively, eachfiber can have a flat ribbon shape with a thickness approximately in therange 0.025 mm to 0.5 mm and a width of approximately 0.75 mm to 10 mm.Other suitable shape memory alloys include Ag—Cd, Au—Cd, Au—Cu—Zn,Cu—Al, Cu—Al—N, Cu—Zn, Cu—Zn—Al, Cu—Zn—Ga, Cu—Zn—Si, Cu—Zn—Sn, Fe—Pt,Fe—Ni, In—Cd, In—Ti, Ti—Nb, and Ti—Ni.

Referring to FIGS. 2A and 2B, there are shown graphs of the timeresponse of the fibers 42 made from NiTi. Shown in FIG. 2A is theresponse of a fiber subjected to a strain of nearly 5%. As can be seen,the contraction time for this fiber is about 10 ms. By way of contrast,FIG. 2B illustrates a fiber subjected to faster pulse than that appliedto the fiber of FIG. 2A. With the faster pulse, the fiber experiences astrain of about 1%, while the contraction time is about 1 ms.

In use, the device 10 is typically mounted within applicator that isheld by an operator. The applicator is shaped as a pistol, cylinder orany other suitable geometry. Before the operator activates the device10, magnetic forces hold the piston 20 and the horn 18 together in amanner such that the end section 36 of the piston 20 is seated and incontact with the tapered section 32 of the horn 18.

The operator positions the applicator such that a surface 60 of the horn18 is placed against the skin of an animal such as a pig and turns onthe device 10 with the switch 57. The operator then triggers the device10 such that the controller 38 closes the switch 56 to allow the supercapacitor 53 to discharge thereby applying a potential to the fibers 42which causes them to contract. Hence, as the fibers 42 contract theypull the piston 20 away from the horn 18 to define the chamber 12between the tapered section 32 of the horn and the end section 36 of thepiston. The controller 39 simultaneously instructs the valve 38 to opento allow the drug to flow from the reservoir 14 through the inlet port28 into the chamber 12. After a prescribed period of time, thecontroller 39 directs the valve 38 to close so that a desired amount ofthe drug is held in the chamber 12 for a single injection.

Next, the switch 56 is opened so that the as the batteries 55 rechargethe super capacitor 53, the potential to the fibers 42 is withdrawn, andthe fibers 42 relax. As this occurs, because of the magnetic attractionbetween the horn 18 and the piston 20, the end section 36 of the piston20 accelerates towards the tapered section 32. As the end section 36 andthe tapered section 32 come closer together, the volume of the chamber12 is reduced thereby expelling the drug from the chamber 12 through theorifice 13 into the skin. Note that as the end section 36 and thetapered section 32 come together, the injection pressure applied to thedrug through the orifice 13 increases since the speed at which endsection 36 moves toward the tapered section 32 increases inversely withthe square of the distance between the two. In addition, the particularshape of the tapered section 32 narrows down the acoustic wave toprovide higher amplification. The injection pressure is at least 1 MPaand can be as high as 300 MPa.

The batteries 55 recharge the super capacitor 53 for the next injection,while the operator removes the applicator from the animal and begins theprocess with a new animal. In the present application, the reservoir 14contains enough of the drug for about 100 to 200 injections. When thereservoir 14 is depleted, the operator picks up another applicator tocontinue with the process. Alternatively, the reservoir 14 can be aremovable cartridge that the operator easily exchanges with anothercartridge filled with the drug.

While this invention has been particularly shown and described withreferences to preferred embodiments thereof, it will be understood bythose skilled in the art that various changes in form and details may bemade therein without departing from the scope of the inventionencompassed by the appended claims. For example, in an alternativeembodiment, the horn 18 is provided with a pressure or force sensor 100(FIG. 1) so that the entire injection process described above isautomatically triggered. In such an implementation, the operator merelyplaces the surface 60 of the horn 18 against the skin and when thesensor 100 detects that there is an appropriate contact force orpressure between the skin and the surface 60, the device 10 is triggeredto inject the drug into the animal and subsequently re-cocks or re-loadsfor the next animal. In yet another alternative embodiment, contractilepolymers, or any other suitable contracting material, can be usedinstead of the shape memory alloy.

1. An injector, comprising: a housing having a chamber for holding aliquid formulation of an active principle to be injected into abiological body and an output port in fluid communication with thechamber, the liquid fomulation being injected through the output port; apiston positioned within the housing, the piston including an endportion with substantially the same shape as the chamber; and anactuator attached to the piston and adapted to force the piston awayfrom the housing in opposition to a magnetic force, the piston andhousing being drawn together by a magnetic force in response to theactuator relaxing its force on the piston to expel the liquidformulation out of the chamber through the output port.
 2. The injectorof claim 1 further comprising an inlet port for filling the chamber withthe liquid formulation.
 3. The injector of claim 1 wherein the actuatoris made of a shape memory alloy, the actuator moving the piston awayfrom the housing when a potential is applied to the actuator, and thepiston moving towards the housing when the voltage is removed.
 4. Theinjector of claim 3 wherein the actuator is one or more fibers of theshape memory alloy.
 5. The injector of claim 3 wherein the shape memoryalloy is Ni—Ti.
 6. The injector of claim 3 wherein the shape memoryalloy is approximately 10 mm to 200 mm long.
 7. The injector of claim 6wherein the shape memory alloy contracts approximately 0.5 mm to 10 mmwhen the potential is applied to the alloy.
 8. The injector of claim 3wherein the shape memory alloy structure changes phase from martensiteto austenite when the potential is applied to the alloy.
 9. The injectorof claim 3 further comprising a capacitor, wherein the potential isapplied to the actuator when the capacitor discharges.
 10. The injectorof claim 9 wherein the capacitor has an energy output of about 100 J.11. The injector of claim 9 wherein the capacitor has an energy outputof at least about 10 J.
 12. The injector of claim 1 wherein the injectorhas a maximum injection pressure of approximately 300 MPa.
 13. Theinjector of claim 1 wherein the injector has an injection pressure of atleast 1 Mpa.
 14. The injector of claim 1 wherein the injector has acycle time of about one sec.
 15. The injector of claim 1 wherein theoutput port has a diameter of about 50 μm to 200 μm.
 16. The injector ofclaim 1 wherein the chamber has a tapered shape.
 17. The injector ofclaim 1 wherein the liquid formulation is a drug.
 18. The injector ofclaim 1 further comprising an actuator attached to the piston and madeof contractile polymers, the actuator moving the piston away from thehousing when a potential is applied to the actuator, and the pistonmoving towards the housing when the voltage is removed.
 19. The injectorof claim 1 further comprising an actuator attached to the piston andmade of a contracting material, the actuator moving the piston away fromthe housing when a potential is applied to the actuator, and the pistonmoving towards the housing when the voltage is removed.
 20. An injector,comprising: a housing having a chamber for holding a liquid formulationof an active principle to be injected into a biological body and anoutput port in fluid communication with the chamber, the liquidformulation being injected though the output port; a piston positionedwithin the housing, the piston including an end portion withsubstantially the same shape as the chamber; and an actuator attached tothe piston and made of shape memory alloy, the piston and housing beingdrawn together by a magnetic force, the actuator moving the piston awayfrom the housing when a potential is applied to the actuator, and thepiston moving towards the housing when the voltage is removed to expelthe liquid formulation out of the chamber through the output port. 21.An injector, comprising: a housing having a chamber for holding a liquidformulation of an active principle to be injected into a biological bodyand an output port in fluid communication with the chamber, the liquidformulation being injected through the output port; and a pistonpositioned within the housing, the piston including an end portion withsubstantially the same shape as the chamber, the piston and housingbeing drawn together by a magnetic force to expel the liquid formulationout of the chamber through the output port; and an actuator attached tothe piston and made of shape memory alloy, the actuator moving thepiston away from the housing when a potential is applied to theactuator, and the piston moving towards the housing when the voltage isremoved.
 22. The injector of claim 21 wherein the actuator is one ormare fibers of the shape memory alloy.
 23. The injector of claim 21wherein the shape memory alloy is Ni—Ti.
 24. The injector of claim 21wherein the shape memory alloy is approximately 10 mm to 200 mm long.25. The injector of claim 24 wherein the shape memory alloy contractsapproximately 0.5 mm to 10 mm when the potential is applied to thealloy.
 26. The injector of claim 21 wherein the shape memory alloystructure changes phase from martensite to austenite when the potentialis applied to the alloy.
 27. The injector of claim 21 further comprisinga capacitor, wherein the potential is applied to the actuator when thecapacitor discharges.
 28. The injector of claim 27 wherein the capacitorhas an energy output of about 100 J.
 29. The injector of claim 27wherein the capacitor has an energy output of at least about 10 J. 30.An injector, comprising: a housing having a chamber for holding a liquidformulation of an active principle to be injected into a biological bodyand an output port in fluid communication with the chamber, the liquidformulation being injected through the output port; a piston positionedwithin the housing, the piston including an end portion withsubstantially the same shape as the chamber; and an actuator attached tothe piston and made of contractile polymers, the actuator moving thepiston away from the housing when a potential is applied to theactuator, and the piston moving towards the housing when the voltage isremoved, the piston and housing being drawn together by a magnetic forceto expel the liquid formulation out of the chamber through the outputport.
 31. An injector, comprising: a housing having a chamber forholding a liquid formulation of an active principle to be injected intoa biological body and an output port in fluid communication with thechamber, the liquid formulation being injected through the output port;a piston positioned within the housing, the piston including an endportion with substantially the same shape as the chamber; and anactuator attached to the piston and made of a contracting material, theactuator moving the piston away from the housing when a potential isapplied to the actuator, and the piston moving towards the housing whenthe voltage is removed, the piston and housing being drawn together by amagnetic force to expel the liquid formulation out of the chamberthrough the output port.
 32. The injector of claim 1, wherein themagnetic force is supplied by a permanent magnet.